Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Harbin Medical University, Harbin 150081, China.
Mol Biol Rep. 2011 Mar;38(3):1741-7. doi: 10.1007/s11033-010-0288-7. Epub 2010 Sep 29.
Fbxw8 is the F-box component of a SCF-like E3 ubiquitin ligase complex. Mice lacking Fbxw8 exhibit pathological defects in placenta and embryo similar to fetal growth retardation, suggesting a role of Fbxw8 in placentation. Proliferative capacity of trophoblast cells is very important in placental development. In this context, we revealed that Fbxw8 was expressed in four different human trophoblast cell lines. Silencing of Fbxw8 expression by siRNA inhibited the growth of choriocarcinoma JEG-3 cells. By Western blotting, cell cycle analysis, we showed that down-regulation of Fbxw8 by RNAi induced cell-growth arrest at G2/M phase through decreasing the levels of CDK1, CDK2, cyclin A and cyclin B1 and up-regulation of p27 at protein level. Conversely, over-expression of Fbxw8 led to the opposite effect. These results suggest that Fbxw8 plays an essential role in the proliferation of human trophoblast cells, especially JEG-3 cells, via G2/M phase transition in association with regulation of CDK1, CDK2, cyclin A, cyclin B1 and p27 expression.
Fbxw8 是一种 SCF 样 E3 泛素连接酶复合物的 F 盒组件。缺乏 Fbxw8 的小鼠在胎盘和胚胎中表现出类似胎儿生长迟缓的病理性缺陷，表明 Fbxw8 在胎盘形成中起作用。滋养细胞的增殖能力对于胎盘发育非常重要。在这方面，我们发现 Fbxw8 在四种不同的人滋养层细胞系中表达。通过 siRNA 沉默 Fbxw8 的表达抑制绒毛膜癌细胞 JEG-3 的生长。通过 Western blot 分析、细胞周期分析，我们表明通过降低 CDK1、CDK2、细胞周期蛋白 A 和细胞周期蛋白 B1 的水平和上调 p27 蛋白水平，RNAi 下调 Fbxw8 诱导细胞在 G2/M 期停滞。相反，过表达 Fbxw8 导致相反的效果。这些结果表明，Fbxw8 通过调节 CDK1、CDK2、细胞周期蛋白 A、细胞周期蛋白 B1 和 p27 的表达，在人滋养层细胞，特别是 JEG-3 细胞的增殖中发挥重要作用，特别是在 G2/M 期过渡中。
